Gabriela Silva

Capsaicin induces de-differentiation of activated hepatic stellate cell

Hepatic stellate cells (HSC) play a key role in liver fibrogenesis. Activation of PPARγ and inhibition of fibrogenic molecules are potential strategies to block HSC activation and differentiation. A number of natural products have been suggested to have antifibrotic effects for the de-activation and de-differentiation of HSCs. The purpose of this study was to investigate the in vitro effects of capsaicin on HSC de-activation and de-differentiation. The results demonstrated that capsaicin induced quiescent phenotype in GRX via PPARγ activation. Significant decrease in COX-2 and type I collagen mRNA expression was observed in the first 24 h of treatment. These events preceded the reduction of TGF-β1 and total collagen secretion. Thus, capsaicin promoted down-regulation of HSC activation by its antifibrotic and anti-inflammatory actions. These findings demonstrate that capsaicin may have potential as a novel therapeutic agent for the treatment of liver fibrosis.

Catechin attenuates activation of hepatic stellate cells

(+)‐Catechin is a type of catechin present in large amounts in açaí fruits and cocoa seeds. Besides its antioxidant and anti‐inflammatory activities, little is known about its effects in the liver, especially during hepatic fibrosis. We report here the effects of (+)‐catechin on hepatic stellate cells. (+)‐Catechin induced quiescent phenotype in GRX cells, along with an increase in lipid droplets. Proliferator‐activated receptor γ mRNA expression was upregulated, whereas type I collagen mRNA expression was downregulated. Pro‐inflammatory cytokines were not influenced by (+)‐catechin, whereas the levels of interleukin 10 were significantly increased. The data provide evidence that (+)‐catechin can reduce hepatic stellate cell activation.

Immediate Effects of Chest Physiotherapy on Hemodynamic, Metabolic, and Oxidative Stress Parameters in Subjects With Septic Shock

BACKGROUND: Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. METHODS: We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 μg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy. RESULTS: Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6–10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and PaCO2 (P = .008); reduction of lactate (P = .001); and an increase in PaO2 (P = .03), arterial oxygen saturation (P = .02), and PaO2/FIO2 (P = .034), 15 min after it was applied. CONCLUSIONS: The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters.

N-acetylcysteine and fructose-1,6-bisphosphate: immunomodulatory effects on mononuclear cell culture

INTRODUCAO: A sepse e uma sindrome complexa causada pela resposta inflamatoria sistemica descontrolada. As citocinas inflamatorias representam papel central na patogenese do choque septico. Tem sido testadas estrategias terapeuticas a fim de modular a geracao ou a funcao excessiva de mediadores na sepse. OBJETIVO: O objetivo deste estudo foi investigar o efeito terapeutico da N-acetilcisteina (NAC) e sua associacao com a frutose-1,6-bisfosfato (FBP) sobre a proliferacao de linfocitos T e a geracao de interleucina-1β (IL-1β) e proteina quimiotatica de monocitos 1 (MCP-1) em cultura celular. MATERIAL E METODOS: Foram isoladas celulas mononucleares de sangue periferico de individuos saudaveis. Os linfocitos T foram estimulados por 96 horas com fitohemaglutinina e submetidos a diferentes concentracoes de NAC ou NAC associada a FBP (1,25 mM). RESULTADOS: O tratamento com NAC (10 e 15 mM) ou NAC (15 mM) associado a FBP reduziu a proliferacao celular. Os niveis de IL-1β aumentaram com a presenca de NAC (15 mM) e NAC + FBP. A concentracao de MCP-1 mostrou-se reduzida apenas no grupo tratado com NAC associada a FBP. CONCLUSAO: Os resultados sugerem que tanto a NAC quanto a NAC associada a FBP sao capazes de inibir a proliferacao celular, atuando como potentes agentes imunomoduladores, sugerindo seu uso em doencas inflamatorias.

Antifibrotic effect of Pluchea sagitallis (Lam.) cabrera aqueous extract in grx cell lineage

Liver fibrosis is a complex disease that is caused by inappropriate tissue repair due to the deposition of connective tissue. When a chronic lesion affects the liver, regenerative response fails and hepatocytes are replaced with abundant extracellular matrix (ECM). The imbalance between production and degradation of ECM will result in the accumulation of proteins that change normal liver architecture, and thus its functionality. The main source of ECM is the activated hepatic stellate cell (HSC). In order, to clarify possible therapeutic approaches to the disease, this work aimed to evaluate the possible antifibrotic action of Pluchea sagitallis (Lam.) Cabrera on an activated HSC immortalized lineage (GRX). Our results demonstrated that the P. sagittalis aqueous extract at 0.039 and 0.078 mg/mL concentrations was able to reduce cell growth and proliferation. Regarding to oxidative stress evaluation, there was no statistically significant difference between the treated group and the control. Staining with OilRed-O (ORO) showed a statistically significant increase in intracellular lipid content after 5 days of treatment, exerting in vitro effect on the GRX phenotypic change of activated towards the quiescent state. These results were confirmed by colorimetric quantification of lipid content. Regarding the TGF-β1 and collagen production, there were no statistically significant differences observed between the groups. In conclusion, the P. sagittalis aqueous extract reduces the growth and proliferation of GRX cells and induces the reversal of activated towards a quiescent phenotype. There was no decrease in cell proliferation either by necrosis or by apoptosis via activation of the senescence. Thus, our data suggest that the extract showed an antifibrotic effect, possibly by activating phenotype reversal.